Our long range objective is to determine the three-dimensional structures of biologically and medically relvant proteins of the vascular system. These proteins are involved in the transport and recycling of vital materials in the body and in the immune system. Crystals of the human haptoglobin-hemoglobin complex have been obtained which are space group P6 sub 2 22 or P6 sub 4 22, a equals 162 Angstroms and c equals 430 Angstroms, two molecules per asymmetric unit, and diffract to 6 Angstrom resolution. X-ray crystallographic, biochemical, and model building techniques are being applied to the complex. The structural basis for the extremely strong contact between these two proteins will be determined. It may help to explain the elevated haptoglobin levels in heart disorders and cancers. The myeloma protein, IgG supra Gar which binds riboflavin strongly, will be studied by electron microscopy, X-ray diffraction, biochemical, and model building methods. Two-dimensional crystals have been obtained of the Fab fragment. The structure of the riboflavin binding site will be elucidated. This molecule may prove to be a good model for a genuine in vivo human antigen-antibody interaction. Methods are being devloped for constructing accurate atomic coordinates for a protein by building its sequence into a known homologous structure. In this way, haptoglobin heavy chain is being constructed from the homologous serine proteases and IgG supra Gar Fab from the other known Fab structures. Using these constructed coordinates, the haptoglobin-hemoglobin and IgG supra Gar-riboflavin interactions are being studied using surface representatives of these molecules.